Louise Murray1, Joseph Longo2, Jonathan Wan1, Caroline Chung1, Lisa Wang3, Laura Dawson1, Michael Milosevic1, Amit Oza4, Anthony Brade5. 1. Department of Radiation Oncology, University of Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. 2. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Canada. 3. Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Canada. 4. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. 5. Department of Radiation Oncology, University of Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. Electronic address: Anthony.Brade@thp.ca.
Abstract
BACKGROUND AND PURPOSE: To evaluate the tolerability and maximum tolerated dose (MTD) of sorafenib administered concurrently with palliative radiotherapy. MATERIAL AND METHODS: In patients with incurable cancer, sorafenib was escalated independently in three cohorts based on irradiation site: thorax, abdomen or pelvis. Sorafenib was administered days 1-28 and radiotherapy (30Gy in 10 fractions) was delivered days 8-12 and 15-19. Dose-limiting toxicities (DLT) were acute grade 3+ toxicities attributable to radiotherapy. RESULTS: For the thorax, abdomen and pelvis cohorts, 14, 16 and 4 patients were recruited, and Dose Levels 3, 3 and 2 were reached, respectively. Sorafenib-related systemic toxicity led to significant sorafenib interruption in 10 patients. There were 3 DLTs in total, one per cohort: grade 3 oesophagitis (thoracic), transaminase elevation (abdominal) and grade 5 bowel perforation (pelvic; patient with tumour invading bowel). Grade 2 radiation dermatitis developed in 12 patients. The trial was terminated early as slow accrual and sorafenib-related systemic toxicity prevented efficient evaluation of RT-related DLTs. CONCLUSIONS: The MTD of sorafenib when used with 30Gy in 10 fractions was not established due to sorafenib-related systemic toxicity. Severe radiotherapy-related toxicities were also observed. These events suggest this concurrent combination does not warrant further study.
BACKGROUND AND PURPOSE: To evaluate the tolerability and maximum tolerated dose (MTD) of sorafenib administered concurrently with palliative radiotherapy. MATERIAL AND METHODS: In patients with incurable cancer, sorafenib was escalated independently in three cohorts based on irradiation site: thorax, abdomen or pelvis. Sorafenib was administered days 1-28 and radiotherapy (30Gy in 10 fractions) was delivered days 8-12 and 15-19. Dose-limiting toxicities (DLT) were acute grade 3+ toxicities attributable to radiotherapy. RESULTS: For the thorax, abdomen and pelvis cohorts, 14, 16 and 4 patients were recruited, and Dose Levels 3, 3 and 2 were reached, respectively. Sorafenib-related systemic toxicity led to significant sorafenib interruption in 10 patients. There were 3 DLTs in total, one per cohort: grade 3 oesophagitis (thoracic), transaminase elevation (abdominal) and grade 5 bowel perforation (pelvic; patient with tumour invading bowel). Grade 2 radiation dermatitis developed in 12 patients. The trial was terminated early as slow accrual and sorafenib-related systemic toxicity prevented efficient evaluation of RT-related DLTs. CONCLUSIONS: The MTD of sorafenib when used with 30Gy in 10 fractions was not established due to sorafenib-related systemic toxicity. Severe radiotherapy-related toxicities were also observed. These events suggest this concurrent combination does not warrant further study.
Authors: Karen S Cortés-Mateus; Katarzyna Holub; Fabricio Racca; Juan José Grau; Jaume Capdevila Journal: Oncol Lett Date: 2018-07-04 Impact factor: 2.967